Related Experiment Video
Updated: Mar 9, 2026
Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice
Kai Fu1, Xin Sun1, Eric M Wier1
1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Abstract:
Previously we reported that Src-associated-substrate-during-mitosis-of-68kDa (Sam68/KHDRBS1) is pivotal for DNA damage-stimulated NF-κB transactivation of anti-apoptotic genes (Fu et al., 2016). Here we show that Sam68 is critical for genotoxic stress-induced NF-κB activation in the γ-irradiated colon and animal and that Sam68-dependent NF-κB activation provides radioprotection to colon epithelium in vivo. Sam68 deletion diminishes γ-irradiation-triggered PAR synthesis and NF-κB activation in colon epithelial cells (CECs), thus hampering the expression of anti-apoptotic molecules in situ and facilitating CECs to undergo apoptosis in mice post whole-body γ-irradiation (WBIR). Sam68 knockout mice suffer more severe damage in the colon and succumb more rapidly from acute radiotoxicity than the control mice following WBIR. Our results underscore the critical role of Sam68 in orchestrating genotoxic stress-initiated NF-κB activation signaling in the colon tissue and whole animal and reveal the pathophysiological relevance of Sam68-dependent NF-κB activation in colonic cell survival and recovery from extrinsic DNA damage.
Insights
Src-associated-substrate-during-mitosis-of-68kDa (Sam68) is crucial for activating NF-κB signaling in response to DNA damage. This pathway protects colon cells from radiation injury, highlighting Sam68
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Src-associated-substrate-during-mitosis-of-68kDa (Sam68/KHDRBS1) was previously identified as vital for DNA damage-stimulated NF-κB transactivation of anti-apoptotic genes.
- The role of Sam68 in genotoxic stress response within the colon and its impact on radioprotection remained to be elucidated.
Purpose of the Study:
- To investigate the critical role of Sam68 in genotoxic stress-induced NF-κB activation in the colon.
- To determine if Sam68-dependent NF-κB activation confers radioprotection to the colon epithelium in vivo.
- To elucidate the pathophysiological relevance of Sam68 in colonic cell survival following DNA damage.
Main Methods:
- Utilized whole-body γ-irradiation (WBIR) in Sam68 knockout and control mice.
- Assessed NF-κB activation, poly(ADP-ribose) (PAR) synthesis, and expression of anti-apoptotic molecules in colon epithelial cells (CECs).
- Evaluated colonic damage and survival rates post-WBIR.
Main Results:
- Sam68 deletion significantly diminished γ-irradiation-triggered PAR synthesis and NF-κB activation in CECs.
- Sam68 deficiency led to reduced expression of anti-apoptotic molecules and increased CEC apoptosis post-WBIR.
- Sam68 knockout mice exhibited more severe colon damage and succumbed more rapidly to acute radiotoxicity compared to controls.
Conclusions:
- Sam68 is critical for orchestrating genotoxic stress-initiated NF-κB activation signaling in the colon tissue and the whole animal.
- Sam68-dependent NF-κB activation plays a crucial role in colonic cell survival and recovery from DNA damage.
- Sam68 is a key mediator of radioprotection in the colon epithelium.
